Background: The prognosis of human glioma is poor, and the highly invasive nature of the disease represents a major impediment to current therapeutic modalities. The oncoprotein B-cell-specific Moloney murine leukemia virus integration site 1 protein (Bmi-1) has been linked to the development and progression of glioma; however, the biological role of Bmi-1 in the invasion of glioma remains unclear. Methods: A172 and LN229 glioma cells were engineered to overexpress Bmi-1 via stable transfection or to be silenced for Bmi-1 expression using RNA interfering method. Migration and invasiveness of the engineered cells were assessed using wound healing assay, Transwell migration assay, Transwell matrix penetration assay and 3-D spheroid invasion assay. MMP-9 expression and activity were measured using real-time PCR, ELISA and the gelatin zymography methods. Expression of NF-kappaB target genes was quantified using real-time PCR. NF-kappaB transcriptional activity was assessed using an NF-kappaB luciferase reporter system. Expression of Bmi-1 and MMP-9 in clinical specimens was analyzed using immunohistochemical assay. Results: Ectopic overexpression of Bmi-1 dramatically increased, whereas knockdown of endogenous Bmi-1 reduced, the invasiveness and migration of glioma cells. NF-kappaB transcriptional activity and MMP-9 expression and activity were significantly increased in Bmi-1-overexpressing but reduced in Bmi-1-silenced cells. The reporter luciferase activity driven by MMP-9 promoter in Bmi-1-overexpressing cells was dependent on the presence of a functional NF-kappaB binding site, and blockade of NF-kappaB signaling inhibited the upregulation of MMP-9 in Bmi-1 overexpressing cells. Furthermore, expression of Bmi-1 correlated with NF-kappaB nuclear translocation as well as MMP-9 expression in clinical glioma samples. Conclusions: Bmi-1 may play an important role in the development of aggressive phenotype of glioma via activating the NF-kappaB/MMP-9 pathway and therefore might represent a novel therapeutic target for glioma.

Original Article Laboratory blood test profiling reveals distinct biochemical and hemocyte features of KRAS mutated non-small cell lung cancer Limin Ou, Xiuyu Cai, Wenchuang Zeng, Liyan Huang, Qiuhua Deng, Hailing Tang, Zhuxing Chen, Huan Zhou, Yongping Lin, Liping Liu, Wenhua Liang

Background: Pulmonary ground-glass opacity (GGO) is often considered to have inert biological behavior. However, whether the clinicopathological features and aggressiveness of GGO associated with cystic airspace (GGO-A) differ from GGO associated without cystic airspace (GGO-nA) remains unknown. This study aimed to compare the clinicopathological features and aggressiveness of GGO-A with GGO-nA. Methods: This retrospective study included patients with GGOs [lesion size: 0.5–2.0 cm, consolidation-to-tumor ratio (CTR) ≤50%] from 2017 to 2021. Patients were divided into GGO-As and GGO-nAs. Chi-squared, Mann-Whitney test, Kaplan-Meier analyses and Logistic regression were utilized for data analysis. Results: A total of 818 patients (266 with GGO-As and 552 with GGO-nAs) were enrolled. Compared to patients with GGO-nAs, patients with GGO-As had distinct clinical features: male [odds ratio (OR) =5.588, P<0.001], without family history of cancer (OR =5.121, P<0.001), with emphysema pulmonum (OR =3.228, P=0.003) and with pulmonary bullae (OR =2.634, P<0.001). Compared to GGO-nAs, GGO-As had more invasive adenocarcinomas (IAs) (75.8% vs. 39.3%, P<0.001) and micropapillary subtypes (17.0% vs. 5.7%, P=0.09). In addition, KRAS mutated more frequently in GGO-As than GGO-nAs (15.5% vs. 2.5%, P=0.07). Among patients followed up, there were higher frequency of GGO growth (28.9% vs. 17.0%, P=0.02) and shorter median time from baseline to GGO growth (24.0 months vs. not reached, log rank P<0.001) in GGO-As than GGO-nAs. Furthermore, among pure-GGOs and non-smokers, GGO-As were still associated with higher aggressiveness. Conclusions: GGO-A showed higher aggressiveness compared to GGO-nA, with more invasive histological subtypes, a higher frequency of KRAS mutations, and faster radiological progression. These findings suggested more proactive surveillance and potentially aggressive clinical management for GGO-As.